Analysis of the SORT1 gene in familial amyotrophic lateral sclerosis

Abstract

Background: Substantial efforts have been deployed in the past decade to identify the genetic causes of amyotrophic lateral sclerosis (ALS), and we hypothesized here that mutations in SORT1 or aberrant SORT1 splicing reduce progranulin level and promote neurodegeneration.

Methods: We sequenced the coding exons of SORT1 in a cohort of 112 unrelated individuals with familial ALS. We also tested for aberrant SORT1 splicing by RT-PCR using RNA samples from cell lines expressing six different ALS-associated TARDBP mutations.

Results: We identified one unique missense and two unique silent mutations in our cohort. None are predicted to have functional effects. No aberrant SORT1 splicing event was observed.

Conclusions: SORT1 mutations are not a common cause of familial ALS, and the influence of TARDBP mutations on SORT1 splicing still needs to be clarified.